Registration Dossier

Administrative data

Description of key information

Skin irritation: Not irritating

Eye irritation: Not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
The dermal acute toxicity test includes regular examination of rabbit skin following a single exposure over 14 days. The scoring of skin irritation was performed using the Draize scale. The exposure was conducted on abraded skin under occulsive conditions for 24 hours, a more extreme exposure than current guidelines. As a result the study provides information sufficient to address the skin irritation potential of the test substance.
GLP compliance:
no
Remarks:
Study precedes the development of Good Laboratory Practices
Specific details on test material used for the study:
Described as a clear yellow, slightly viscous liquid with a faint odor
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Four groups of four adult albino rabbits, either sex.
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
50, 200, 794, and 3160 mg/kg of body weight
Duration of treatment / exposure:
24 hours
Observation period:
Dermal irritation recorded at 24 hours and once daily thereafter for a total of 14 days
Number of animals:
16
Details on study design:
The test substance was each administered by a single application to four groups of four rabbits each at dosage levels of 50, 200, 794, and 3160 mg/kg of body weight. The test substance was applied to the closely clipped, abraded abdominal skin of each rabbit beneath a binder of rubber dam. The trunk of each animal was then wrapped in gauze and adhesive tape, and the animals were collared to prevent ingestion of the compound. After an exposure period of 24 hours, the binders and collars were removed, and the abdominal skin was cleansed with corn oil to remove any compound residue.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #7
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #8
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #9
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #10
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #11
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #12
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #13
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #14
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #15
Time point:
24 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal: #16
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
other: desquamation
Basis:
other: Single rabbit not identifed by number
Time point:
other: days 5 and 6
Reversibility:
fully reversible
Remarks:
The observation of desquamation was noted on only two days, but not on later days of the observation period.
Remarks on result:
other: desquamation
Remarks:
desquamation in one rabbit on two days was noted in the report, but the rabbit number was not identified
Irritant / corrosive response data:
Skin irritation was slight and consisted of erythema (moderate in two animals at 3160 mg/kg) in all animals at 24 hours which persisted for two to six days. Desquamation was observed in one "low level" animal on Days 5 and 6.
Interpretation of results:
GHS criteria not met
Conclusions:
The results indicate the test substance does not meet the criteria for skin irritation classification.
Executive summary:

Four groups of four New Zealand White rabbits (identified as males and females, but not with specified distribution) were exposured to 50, 200, 794, and 3160 mg/kg body weight of the test substance on abraded skin for 24 hours under occlusive conditions. Observations of the skin condition were made at 24 hours and daily thereafter for up to 14 days. Mild erythema was noted in all exposed animals at the first examination (24 hour time point), but did not increase in severity or duration with dose. All signs of skin irritation were resolved within six days. The results indicate that exposure to the test substance under conditions more extreme than current guidelines produced mild skins of skin irritation which were fully reversed during the observation period. On that basis the substance does not meet criteria for classification as a skin irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Remarks:
Study precedes the development of Good Laboratory Practices
Specific details on test material used for the study:
Described as a clear yellow, slightly viscous liquid with a faint odor
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Groups of six adult male and female albino rabbits of the New Zealand White variety provided Purina Rabbit Chow and water available ad libitum.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Treated eyes were held closed for one second following application. No rinsing was described in the study report.
Observation period (in vivo):
Seven days
Number of animals or in vitro replicates:
Six rabbits
Details on study design:
The test substance was administered as a single application of 0.1 ml into the conjunctival sac of the left eye of each of six rabbits. Untreated right eyes served as controls.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
80
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
10
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
80
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
10
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
20
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
80
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
10
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
80
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
10
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
20
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
80
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
10
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
80
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
10
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.7
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
20
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Slight conjunctival erythema (moderate in one animal at four hours) subsided by 72 hours. Slight discharge was noted at one hour only. On Day 7, negative fluorescein examination confirmed the absence of corneal damage in all eyes
Other effects:
Blinking and preening noted immediately after instillation of compound.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance produced only slight conjunctival irritation consisting of slight erythema and discharge which completely subsided by 72 hours. The substance does not meet criteria for classification.
Executive summary:

Potential for eye irritation was assessed in a group of six male and female New Zealand White rabbits. Each rabbit received a single instillation of 0.1 mL test substance in the conjunctival sac of one eye (with the other eye consider the control) without subsequent irrigation and were observed for eye irritation for up to seven days. The iris and corneas irritation scores consistently showed no signs of irritation during the observation period. Minor conjunctival indications of irritation (redness) were observed in four of six rabbits at 24 or 48 hours, but resolved by 72 hours in all cases. The substance does not meet criteria for classificaiton as an eye irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin: Based on the results of the available data the substance does not require to be classified and labelled according to Regulation 1272/2008/EC (CLP) or Directive 67/548/EEC (DSD).

Eye: Based on the results of the available data the substance does not require to be classified and labelled according to Regulation 1272/2008/EC (CLP) or Directive 67/548/EEC (DSD).